While soft tissues (e.g., muscle and skin) and bone possess considerable capacity for recovery after injury, inadequate nerve repair frequently limits the extent to which normal function is regained. In the peripheral nervous system (PNS), nerves are often able to regenerate on their own, if the injury is small enough. Larger injuries may be effectively treated surgically, either by direct reconnection of damaged nerve ends with the nerve sheath the axons previously used to reach their destination or with grafts harvested from elsewhere in the body. However, clinical functional recovery rates generally approach only 80% following nerve graft, and the procedure has the additional disadvantage of requiring two surgeries. An alternative approach to nerve repair in the PNS is to provide an artificial conduit, such as the NeuraGen™ Nerve Guide (Integra LifeSciences, Plainsboro, N.J.), a collagen tube providing a conduit for axonal growth across a nerve gap [83]. However, this treatment is typically reserved for small defects (e.g., several millimeters).
Clinical treatment of injuries to the central nervous system (CNS) is considerably less successful. Unlike nerves in the PNS, axons in the CNS do not undergo significant regeneration in their native environment. Thus initial therapy is usually limited to removal of bone fragments to prevent secondary injury and administration of drugs such as corticosteroids to reduce swelling. Currently there is no effective treatment available to completely restore nerve function in the CNS. Rehabilitation, in which patients train remaining nerves to compensate for loss due to injury, remains the mainstay of therapy.
Despite the relatively bleak outlook for regeneration of injured nerves in the CNS, advances in other areas of medical care have greatly improved the rate of survival of patients with traumatic CNS injuries, e.g., traumatic injury to the spinal cord. Nearly 94% of patients with spinal cord injuries survive the first year following injury, and of these, 93% are able to be discharged back into the community [84]. Approximately 10,000-12,000 individuals suffer spinal cord injuries each year in the United States, bringing the projected prevalence rate in the United States to nearly 280,000 by the year 2014 [84].
The number of patients with traumatic spinal cord or brain injury is dwarfed by the number of persons who experience damage to the CNS due to diseases and stroke [85], or as a consequence of conditions such as primary brain tumors, brain metastastes from tumors elsewhere in the body, or surgery for these conditions. Survivors of stroke and survivors of brain lesions due to tumors or surgical damage frequently experience permanent deficits in function due to loss of brain tissue either as a direct consequence of injury or secondary to events such as swelling and/or release of neurotoxic substances from necrotic tissue. While emerging therapies for these patients may offer the potential to limit such damage, prospects for restoring function lost due to death of brain cells and disruption of brain architecture remain poor, and therapeutic efforts focus on rehabilitation.
It is therefore evident that a significant need in the art exists for improved treatments that would enhance repair and regeneration in the CNS. In addition, there remains a need in the art for improved treatments that would enhance nerve repair and regeneration in the PNS since current treatments, while frequently effective, have a number of disadvantages.